Fertility preservation

Chemotherapy and radiation treatments for cancer and other serious illnesses can affect reproductive health. The regimens that threaten ovarian and testicular function are mainly radiation therapy to the pelvic area and some types of chemotherapy. Chemotherapies with high risk include procarbazine and alkylating drugs such as cyclophosphamide, ifosfamide, busulfan, melphalan, chlorambucil and chlormethine.[1] Drugs with medium risk include doxorubicin and platinum analogs such as cisplatin and carboplatin.[1] On the other hand, therapies with low risk of gonadotoxicity include plant derivatives such as vincristine and vinblastine, antibiotics such as bleomycin and dactinomycin and antimetabolites such as methotrexate, mercaptopurine and 5-fluoruracil.[1]

These regimens attack rapidly dividing cells in the body, including healthy cells like sperm and those belonging to the ovarian follicle (egg). Depending on the dose and duration of administration, these therapies can have varying effects on reproductive health. Surgery involving reproductive tissue affects reproductive function and fertility.

For many cancer patients, the decrease or loss of reproductive function is temporary; many men and women, however, do not regain fertility after cancer treatment. Patients undergoing serious radiation, chemotherapy, or surgery sometimes experience symptoms resembling menopause (in women) or andropause (in men), which indicate reproductive damage. In women, decreased estrogen levels as a result of ovarian deficiency lead to weakened bone, changes in temperature control, altered mood, and decreased sexual desire. Men with testicular insufficiency also experience similar symptoms.

A study indicated that fewer oocytes are recovered from cancer patients wanting to perform embryo preservation when compared with an age-matched control group, but the mean number of zygotes generated appears to be similar.[2] The same study found that, of 65 patients referred to the program, 28% declined to undergo embryo, oocyte, or tissue cryopreservation. 9% were found not to be eligible for medical reasons. Of the remaining 41 patients, 85% chose to cryopreserve embryos, 10% chose to cryopreserve oocytes, and 5% chose to undergo ovarian tissue freezing.[2] No serious clinical sequelae resulted from participation.[2]

In women with cancer, a testing for the level of anti-Müllerian hormone (AMH) is useful in predicting the long-term post-chemotherapy loss of ovarian function, in turn predicting the need for fertility preservation strategies.[3]

Fertility preservation, such as ovarian tissue or oocyte cryopreservation, may also be used to prevent infertility, as well as birth defects, associated with advanced maternal age.

Men hoping to preserve their fertility before undergoing treatment for cancer or another fertility-threatening disease can cryopreserve, or freeze, their sperm, which can be obtained through masturbation in post-pubescent boys and men. This is the most established fertility preservation method for males. For pre-pubescent boys, sperm can be obtained through testicular aspiration or electrostimulation and then stored for future use. Researchers are also looking at methods for cryopreserving testicular tissue samples so that they can be re-implanted into the body after treatment.

Some female patients choose to have mature eggs extracted and fertilized outside of the body with sperm from a partner or donor. The resulting embryo is then frozen until the woman is in remission from disease. When the woman is ready to initiate pregnancy, the embryo is thawed and implanted into the uterus for maturation and birth. While this option is the most common fertility preservation method in women, it is not available to pre-pubescent girls, who do not have mature eggs that can be fertilized. Women who do not have a partner will need to use donor sperm. Additionally, because this procedure requires a two-week period of hormonal stimulation to encourage egg maturation, it is not optimal for female patients who are diagnosed with hormone-sensitive cancers (such as breast cancer, ovarian cancer, etc.) or those who cannot delay cancer treatment. Alternative methods of hormonal stimulation using letrozole or tamoxifen may be used for women with hormone-sensitive cancers.

Strips of cortical ovarian tissue can also be cryopreserved, but it must be re-implanted into the body to allow the encapsulated immature follicles to complete their maturation. Furthermore, ovarian tissue is fragile under hard freezing conditions and putting it back into the body carries the risk of re-introducing cancerous cells. In vitro maturation has been achieved experimentally, but the technique is not yet clinically available.[5] With this technique, cryopreserved ovarian tissue could possibly be used to make oocytes that can directly undergo in vitro fertilization.[5]

Many patients diagnosed with a malignancy or another disease requiring treatment that may impair their fertility consider alternatives to bearing biological children, such as assisted reproductive technology (ART) using in vitro fertilization (IVF) with donor eggs or donor sperm. The resulting embryo can be implanted into the woman's uterus after her endometrium (the lining of the uterus) is stimulated with hormones to prepare for the development of the embryo.

In women requiring local pelvic radiation therapy may benefit from surgical transposition of the ovaries to a site remote from maximal radiation exposure.[6][7]

The use of GnRH agonists for ovarian protection during chemotherapy is suggested to benefit the ability to ovulate, but benefits in terms of e.g. pregnancy rate are lacking.[6]